Characteristics of BRAF V600E Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer: A Multicenter Series of 287 Patients

Author:

Fouchardière Christelle1,Cohen Romain2,Malka David3,Guimbaud Rosine4,Bourien Héloïse5,Lièvre Astrid6,Cacheux Wulfran7,Artru Pascal8,François Eric9,Gilabert Marine10,Samalin-Scalzi Emmanuelle11,Zaanan Aziz12,Hautefeuille Vincent13,Rousseau Benoit14,Senellart Hélène15,Coriat Romain16,Flippot Ronan3,Desseigne Françoise1,Lardy-Cleaud Audrey17,Tougeron David18

Affiliation:

1. Medical Oncology Department, Centre Leon Berard, Lyon I University, Lyon, France

2. Medical Oncology Department, AP-HP, Saint-Antoine Hospital, Sorbonne University, Paris, France

3. Gastrointestinal Oncology Unit, Department of Cancer Medicine, Gustave Roussy, Villejuif, France

4. Department of Medical Oncology, University Hospital Toulouse, Paul Sabatier University, Toulouse, France

5. Department of Medical Oncology, Eugène Marquis Cancer Institute, Rennes, France

6. Gastroenterology Department, Rennes University Hospital, Rennes 1 University, Rennes, France

7. Medical Oncology Department, Institut Curie, René Huguenin Hospital, Saint-Cloud, France

8. Gastrointestinal Oncology, Jean-Mermoz Hospital, Lyon, France

9. Gastroenterology Department, Antoine Lacassagne Cancer Centre, Nice, France

10. Medical Oncology Department, Paoli-Calmettes Institute, Aix-Marseille University, Marseille, France

11. Digestive Oncology Department, Montpellier Cancer Institute, Montpellier, France

12. Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Sorbonne Paris Cité, INSERM UMR-S1147, Paris, France

13. Department of Digestive Oncology, Amiens University Hospital, Amiens, France

14. Department of Oncology, Henri Mondor Hospital, AP-HP, Créteil, France

15. René Gauducheau West Cancer Institute, Saint-Herblain, France

16. Gastrointestinal Oncology Unit, CHU Cochin-Port-Royal, Paris, France

17. Clinical Research and Innovation Department, Leon Berard Cancer Centre, Lyon, France

18. Department of Gastroenterology, Poitiers University Hospital, Poitiers, France

Abstract

Abstract Background BRAF V600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown. Materials and Methods We built a multicenter clinico-biological database gathering data from patients with BRAFV600E-mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model. Results We included 287 patients (median age, 67 years [28–95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97–27.04), and median progression-free survival in the first-line setting was 4.34 months (95% CI, 3.81–5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti-epidermal growth factor receptor) were not associated with overall and progression-free survival. Stage IV disease (synchronous metastases) and absence of curative-intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p = .009). Conclusion Despite that BRAFV600E-mutant mCRCs are associated with poor overall and progression-free-survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAFV600E mCRC in day-to-day practice. Implications for Practice Mismatch repair (MMR) testing and resectability discussion in patients with BRAFV600E metastatic colorectal cancer (mCRC) should be performed in day-to-day practice to steer treatment decision making in patients with BRAFV600E-mutant mCRC.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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